2nm0
From Proteopedia
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Crystal Structure of SCO1815: a Beta-Ketoacyl-Acyl Carrier Protein Reductase from Streptomyces coelicolor A3(2)
Overview
Aromatic polyketides are medicinally important natural products produced, by type II polyketide synthases (PKSs). Some aromatic PKSs are bimodular, and include a dedicated initiation module which synthesizes a non-acetate, primer unit. Understanding the mechanism of this initiation module is, expected to further enhance the potential for regiospecific modification, of bacterial aromatic polyketides. A typical initiation module is, comprised of a ketosynthase (KS), an acyl carrier protein (ACP), a, malonyl-CoA:ACP transacylase (MAT), an acyl-ACP thioesterase, a, ketoreductase (KR), a dehydratase (DH), and an enoyl reductase (ER). Thus, far, the identities of the ketoreductase, dehydratase, and enoyl reductase, remain a mystery because they are not encoded within the PKS biosynthetic, gene cluster. Here we report that SCO1815 from Streptomyces coelicolor, A3(2), an uncharacterized homologue of a NADPH-dependent ketoreductase, recognizes and reduces the beta-ketoacyl-ACP intermediate from the, initiation module of the R1128 PKS. SCO1815 exhibits moderate specificity, for both the acyl chain and the thiol donor. The X-ray crystal structure, of SCO1815 was determined to 2.0 A. The structure shows that SCO1815, adopts a Rossmann fold and suggests that a conformational change occurs, upon cofactor binding. We propose that a positively charged patch formed, by three conserved residues is the ACP docking site. Our findings provide, new engineering opportunities for incorporating unnatural primer units, into novel polyketides and shed light on the biology of yet another, cryptic protein in the S. coelicolor genome.
About this Structure
2NM0 is a Single protein structure of sequence from Streptomyces coelicolor. Active as [acyl-carrier-protein_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number 1.1.1.100 Full crystallographic information is available from OCA.
Reference
Structural and functional studies on SCO1815: a beta-ketoacyl-acyl carrier protein reductase from Streptomyces coelicolor A3(2)., Tang Y, Lee HY, Tang Y, Kim CY, Mathews I, Khosla C, Biochemistry. 2006 Nov 28;45(47):14085-93. PMID:17115703 [[Category: 3-oxoacyl-[acyl-carrier-protein] reductase]]
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